Cells become more susceptible to disease as they age, and thus understanding the fundamental molecular mechanisms that regulate aging is important to public health. Aging cells undergo profound shifts in gene expression that are regulated, in part, by epigenetic changes. These epigenetic alterations include histone methylation and acetylation as well as cytosine methylation. The modified epigenetic state results in the expression of genes needed for protection during cell death (antioxidant genes) as well as inappropriate expression of normally silenced regions. The long-term goal of this project is to demonstrate the importance of epigenetic changes that accompany leaf senescence in Arabidopsis thaliana. Specific aims include the analysis of potential regulatory genes that show both an increase in gene expression and a gain in the histone 3 lysine 4 trimethylation (H3K4me3) mark to determine if primary response genes are marked by H3K4me3. Critical histone modifiers will be identified by genetic analysis using altered gene expression as the selective criteria. In addition, the loss of cytosine methylation during aging will be tested for u-regulated genes and one up-regulated transposon. Although the model organism is a plant, many of the same protective genes (i.e. glutathione) are expressed in plants and animals, and silencing of repetitive DNA regions is essential for the genome integrity of both plants and animals.